SETD2 Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR). Acts as a tumor suppressor. H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A. H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase. Required during angiogenesis. Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3. In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1. Trimethylates 'Lys-40' of alpha-tubulins such as TUBA1B (alpha-TubK40me3); alpha-TubK40me3 is required for normal mitosis and cytokinesis and may be a specific tag in cytoskeletal remodeling. Involved in interferon-alpha-induced antiviral defense by mediating both monomethylation of STAT1 at 'Lys-525' and catalyzing H3K36me3 on promoters of some interferon-stimulated genes (ISGs) to activate gene transcription. (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily. Ubiquitously expressed. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Amino Acid Metabolism - lysine degradation; EC; Methyltransferase; Methyltransferase, protein lysine
Chromosomal Location of Human Ortholog: 3p21.31
Cellular Component:  chromosome; nucleoplasm; nucleus
Molecular Function:  alpha-tubulin binding; histone methyltransferase activity (H3-K36 specific); histone-lysine N-methyltransferase activity; metal ion binding; protein binding; protein-lysine N-methyltransferase activity
Biological Process:  angiogenesis; cell migration involved in vasculogenesis; coronary vasculature morphogenesis; defense response to virus; embryonic cranial skeleton morphogenesis; embryonic placenta morphogenesis; endodermal cell differentiation; forebrain development; histone H3-K36 dimethylation; histone H3-K36 trimethylation; mesoderm morphogenesis; microtubule cytoskeleton organization involved in mitosis; mismatch repair; morphogenesis of a branching structure; neural tube closure; nucleosome organization; peptidyl-lysine monomethylation; peptidyl-lysine trimethylation; pericardium development; positive regulation of interferon-alpha production; regulation of cytokinesis; regulation of double-strand break repair via homologous recombination; regulation of mRNA export from nucleus; regulation of protein localization to chromatin; regulation of transcription, DNA-templated; response to type I interferon; stem cell development; stem cell differentiation; transcription elongation from RNA polymerase II promoter
Disease: Luscan-lumish Syndrome
Reference #:  Q9BYW2 (UniProtKB)
Alt. Names/Synonyms: FLJ16420; FLJ22472; FLJ23184; FLJ45883; FLJ46217; HBP231; HIF-1; HIF1; HIP-1; Histone-lysine N-methyltransferase SETD2; hSET2; HSPC069; huntingtin interacting protein 1; Huntingtin yeast partner B; Huntingtin-interacting protein 1; Huntingtin-interacting protein B; HYPB; KIAA1732; KMT3A; Lysine N-methyltransferase 3A; p231HBP; SET domain containing 2; SET domain-containing protein 2; SET2; SETD2
Gene Symbols: SETD2
Molecular weight: 287,597 Da
Basal Isoelectric point: 5.8  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene